Androgen Receptor Network in Prostate Cancer (Homo sapiens)

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SWI/SNF13Apoptotic PathwaysARSPINK1FOXA1MIR21FKBP5SPINK1MYC_HUMANMIR21TRANSLATIONSPRY1TSC1_HUMAN2AR* 3-beta-OH-delta-steroid DH & Steroid isomerase =*** Estradiol-17-beta DH = DHB****HSD3B2CYP17A1HSD3B1HSD3B1HSD17B717-alpha-OH-ProgesteroneDihydrotestosteroneHSD3B1HSD3B1AndrostenedioneHSD3B1Hydroxyprogesterone aldolaseHSD3B1ProgesteroneEstradiolHSD3B2TestosteroneHSD3B1EstroneHSD3B1HSD3B1AndrostenediolHSD3B1F13BGlucocortocoid SynthesisHSD3B1HSD3B1HSD17B4HSD3B1dehydroepiandrosteroneHSD3B1HSD3B1Hydroxyprogesterone aldolaseSteroid-19-HydroxylaseHSD3B2PregnenoloneCYP17A1HSD3B1HSD3B2HSD3B1HSD17B2HSD3B1HSD3B1HSD17B317-alpha-OH-PregnenoloneHSD17B1HSD3B1CholesterolHSD3B1Mineralocortocoid SynthesisSteroid-19-HydroxylaseBASC ComlexRAD50_HUMANOCT1MSH6_HUMANp14CDC2_HUMANp38ATF1ARID1AASK1BRCA1_HUMANCASP8_HUMANPLK1ATR_HUMANBARD1_HUMANCASP9_HUMANCDC25BPUMARB_HUMANSMAD3_HUMANNOXA1_HUMANBLM_HUMANQ8NBS1_HUMANCDK4_HUMANMRE11_HUMANSTAT1_HUMANCDC25ABCL2_HUMANAKT1_HUMANCASP3_HUMANBACH1P53_HUMANCHK2_HUMANp15JAK1_HUMANp27MSH2_HUMANBAX_HUMANp13KPRKDC_HUMANCHK1_HUMANBRCA1_HUMANMMP1_HUMANCDK2_HUMANBAD_HUMANATM_HUMANSMAD2_HUMANE2F1_HUMANMDM2_HUMANp21TMPRSS2KLK3KLK2NDRG1ABCC4TMPRSS2ERGTMPRSS2ETV4SP1ARID1BSMARCA4SMARCC1SMARCC2SMARCD1SMARCD2SMARCD3ACTL6AACTL6BCDC42pathwayTrancriptionPRHOpathwayTranscriptionof Cox2AP-1TranscriptionAnoikisChanges in Cytoskeletonand Cell mobilityRAC1pathwayAKT PathwayMAP2K1MAP4K1STAT3HGFRAP1APTPN11PTENMAP2K2MAPK1CRKLHRASFOSDOCK1PXNRAPGEF1RAF1SOS1MetJUNPTK2BPIK3CAPAK1ELK1MAPK8CRKGAB1RAP1BRASA1GRB2MAPK3TSC2_HUMANRHEB_HUMANMTOR_HUMANRICTORRPTOR_HUMANRPTOR_HUMAN4EBP1_HUMANMYCEIF4EBP1EIF4E1B2CCND1_HUMANSPRY2


Description

The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression. The AR is important for therapeutic target in prostate cancer, thus many different inhibitors have been developed, primarily targeting the ligand binding domain of the protein, while inhibitors that target the N-terminal domain of the protein are still under development. Description source: Wikipedia

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Ontology Terms

 

Bibliography

  1. Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, von Bergen M, Horn F, Brocke-Heidrich K; ''MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4.''; Oncogene, 2011 PubMed
  2. Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM; ''The role of SPINK1 in ETS rearrangement-negative prostate cancers.''; Cancer Cell, 2008 PubMed
  3. Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L, Jiang BH; ''MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression.''; PLoS One, 2011 PubMed

History

View all...
CompareRevisionActionTimeUserComment
98360view06:13, 24 August 2018EgonwUpdated the MIR21 identifier.
98155view13:48, 26 July 2018Fehrhartlayout
96290view15:39, 7 March 2018Fehrhartconnected lines-replace by graphic item
96015view15:04, 15 February 2018MkutmonModified description
96014view15:03, 15 February 2018MkutmonModified description
96013view15:00, 15 February 2018MkutmonModified title
85556view08:33, 29 May 2016EgonwReplaced a mim-conversion with Arrow.
84985view18:49, 4 April 2016AlexanderPicoreplaced mim-conversion with mim-transcription-translation for gene to protein
80439view20:55, 22 June 2015KhanspersAdded mir21 targeting of SMARCA4
80426view18:58, 22 June 2015KhanspersAdded mir21 targeting of PTEN and connected interactions
79838view07:57, 18 April 2015EgonwFixed the metabolite label.
79823view07:44, 17 April 2015EgonwReplaced "EC Number" with "Enzyme Nomenclature" as data source (fixing the links out).
73838view00:09, 26 February 2014MaintBotupdated schema
71495view19:19, 17 October 2013MaintBotUpdated data sources
69730view08:23, 11 July 2013EgonwHydroxyprogesterone aldolase is not a metabolite.
67609view11:32, 26 June 2013DdiglesOntology Term : 'prostate cancer pathway' added !
59165view18:25, 22 February 2013MaintBotUpdated Ensembl data source
54728view19:59, 7 December 2012MaintBotadded p38
54672view21:25, 6 December 2012RobertbaertschPeriodical save, work in progress
54277view20:35, 26 November 2012RobertbaertschPeriodical save, work in progress
54276view20:15, 26 November 2012RobertbaertschPeriodical save, work in progress
54275view19:39, 26 November 2012RobertbaertschPeriodical save, work in progress
54241view08:35, 24 November 2012RobertbaertschPeriodical save, work in progress
53136view01:55, 30 October 2012MaintBotModified categories
50365view22:16, 13 August 2012PgfebboOntology Term : 'prostate cancer' added !
50348view06:01, 13 August 2012Pgfebbomore changes
50347view05:55, 13 August 2012PgfebboPeriodical save, work in progress
50346view05:45, 13 August 2012PgfebboPeriodical save, work in progress
50345view05:35, 13 August 2012PgfebboPeriodical save, work in progress
50344view05:33, 13 August 2012PgfebboMTOR PATHWAY
50302view14:43, 12 August 2012PgfebboPeriodical save, work in progress
50301view14:33, 12 August 2012PgfebboPeriodical save, work in progress
50300view14:18, 12 August 2012PgfebboAdded SPINK1
50269view06:52, 11 August 2012Pgfebbofurther refinement
50268view06:52, 11 August 2012PgfebboPeriodical save, work in progress
50267view06:44, 11 August 2012PgfebboMORE EDITS
50266view06:41, 11 August 2012PgfebboPeriodical save, work in progress
50265view06:31, 11 August 2012PgfebboPeriodical save, work in progress
50264view06:21, 11 August 2012PgfebboPeriodical save, work in progress
50263view06:08, 11 August 2012PgfebboREVISIONS
50262view06:03, 11 August 2012PgfebboPeriodical save, work in progress
50261view05:53, 11 August 2012PgfebboPeriodical save, work in progress
50260view05:43, 11 August 2012PgfebboPeriodical save, work in progress
50259view05:33, 11 August 2012PgfebboPeriodical save, work in progress
50258view05:21, 11 August 2012PgfebboTmprss2 added
50257view05:18, 11 August 2012Pgfebboar to hugo
50075view23:42, 6 August 2012Pgfebborenamed
50073view23:39, 6 August 2012Pgfebbointegrated cancer pathways added
50070view23:34, 6 August 2012PgfebboAdded integrated cancer pathways
50069view23:24, 6 August 2012Pgfebbotrying to add TP53

External references

DataNodes

View all...
NameTypeDatabase referenceComment
17-alpha-OH-PregnenoloneMetaboliteHMDB00363 (HMDB)
17-alpha-OH-ProgesteroneMetaboliteHMDB00374 (HMDB)
4EBP1_HUMANProteinQ13541 (Uniprot-TrEMBL)
ABCC4GeneProduct10257 (Entrez Gene)
ACTL6AGeneProduct86 (Entrez Gene)
ACTL6BGeneProduct51412 (Entrez Gene)
AKT1_HUMANProteinP31749 (Uniprot-TrEMBL)
ARProtein367 (Entrez Gene) AR
ARID1AGeneProduct8289 (Entrez Gene)
ARID1BGeneProduct57492 (Entrez Gene)
ASK1Protein
ATF1GeneProduct466 (Entrez Gene)
ATM_HUMANProteinQ13315 (Uniprot-TrEMBL)
ATR_HUMANProteinQ13535 (Uniprot-TrEMBL)
AndrostenediolMetaboliteHMDB05849 (HMDB)
AndrostenedioneMetabolite63-05-8 (CAS)
BACH1Protein
BAD_HUMANProteinQ92934 (Uniprot-TrEMBL)
BARD1_HUMANProteinQ99728 (Uniprot-TrEMBL)
BAX_HUMANProteinQ07812 (Uniprot-TrEMBL)
BCL2_HUMANProteinP10415 (Uniprot-TrEMBL)
BLM_HUMANProteinP54132 (Uniprot-TrEMBL)
BRCA1_HUMANProteinP38398 (Uniprot-TrEMBL)
CASP3_HUMANProteinP42574 (Uniprot-TrEMBL)
CASP8_HUMANProteinQ14790 (Uniprot-TrEMBL)
CASP9_HUMANProteinP55211 (Uniprot-TrEMBL)
CCND1_HUMANProteinP24385 (Uniprot-TrEMBL)
CDC25AGeneProductENSG00000164045 (Ensembl)
CDC25BGeneProductENSG00000101224 (Ensembl)
CDC2_HUMANProteinP06493 (Uniprot-TrEMBL) Oncogene
CDK2_HUMANProteinP24941 (Uniprot-TrEMBL)
CDK4_HUMANProteinP11802 (Uniprot-TrEMBL)
CHK1_HUMANProteinO14757 (Uniprot-TrEMBL)
CHK2_HUMANProteinO96017 (Uniprot-TrEMBL) Phosphrylated
CRKGeneProduct1398 (Entrez Gene)
CRKLGeneProduct1399 (Entrez Gene)
CYP17A1GeneProduct1586 (Entrez Gene)
CholesterolMetabolite57-88-5 (CAS)
DOCK1GeneProduct1793 (Entrez Gene) Interim Symbol: Dock1 predicted and Name: dedicator of cyto-kinesis 1 (predicted)
DihydrotestosteroneMetaboliteHMDB02961 (HMDB)
E2F1_HUMANProteinQ01094 (Uniprot-TrEMBL)
EIF4E1BProteinA6NMX2 (Uniprot-TrEMBL)
EIF4EBP1GeneProduct1978 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
ELK1GeneProduct2002 (Entrez Gene)
ERGGeneProduct2078 (Entrez Gene) Fusion partner with TMPRSS2 in about 40% of prostate cancers
ETV4GeneProduct2118 (Entrez Gene) Fusion partner with TMPRSS2 in about 40% of prostate cancers
EstradiolMetabolite57-91-0 (CAS)
EstroneMetabolite53-16-7 (CAS)
F13BGeneProduct2165 (Entrez Gene)
FKBP5Protein2289 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene)
FOXA1Protein3169 (Entrez Gene) DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
GAB1GeneProduct2549 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
Glucocortocoid SynthesisPathwayWP237 (WikiPathways)
HGFGeneProduct3082 (Entrez Gene)
HRASGeneProduct3265 (Entrez Gene)
HSD17B1GeneProduct3292 (Entrez Gene)
HSD17B2GeneProduct3294 (Entrez Gene)
HSD17B3GeneProduct3293 (Entrez Gene)
HSD17B4GeneProduct3295 (Entrez Gene)
HSD17B7GeneProduct51478 (Entrez Gene)
HSD3B1GeneProduct3283 (Entrez Gene)
HSD3B2GeneProduct3284 (Entrez Gene)
Hydroxyprogesterone aldolaseGeneProduct4.1.2.30 (Enzyme Nomenclature)
JAK1_HUMANProteinP23458 (Uniprot-TrEMBL)
JUNGeneProduct3725 (Entrez Gene)
KLK2GeneProduct3817 (Entrez Gene)
KLK3GeneProduct354 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAP4K1GeneProduct11184 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MAPK8GeneProduct5599 (Entrez Gene)
MDM2_HUMANProteinQ00987 (Uniprot-TrEMBL) Oncogene
MIR21RnaENSG00000284190 (Ensembl)
MMP1_HUMANProteinP03956 (Uniprot-TrEMBL)
MRE11_HUMANProteinP49959 (Uniprot-TrEMBL)
MSH2_HUMANProteinP43246 (Uniprot-TrEMBL)
MSH6_HUMANProteinP52701 (Uniprot-TrEMBL)
MTOR_HUMANProteinP42345 (Uniprot-TrEMBL)
MYCGeneProduct4609 (Entrez Gene)
MYC_HUMANProteinP01106 (Uniprot-TrEMBL)
MetGeneProduct24553 (Entrez Gene)
Mineralocortocoid SynthesisPathwayWP237 (WikiPathways)
NDRG1GeneProduct10397 (Entrez Gene)
NOXA1_HUMANProteinQ86UR1 (Uniprot-TrEMBL)
OCT1Protein
P53_HUMANProteinP04637 (Uniprot-TrEMBL)
PAK1GeneProduct5058 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PLK1GeneProductENSG00000166851 (Ensembl)
PRKDC_HUMANProteinP78527 (Uniprot-TrEMBL)
PTENGeneProduct5728 (Entrez Gene)
PTK2BGeneProduct2185 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
PUMAProtein
PXNGeneProduct5829 (Entrez Gene)
PregnenoloneMetabolite145-13-1 (CAS)
ProgesteroneMetabolite57-83-0 (CAS)
Q8NBS1_HUMANProteinQ8NBS1 (Uniprot-TrEMBL)
RAD50_HUMANProteinQ92878 (Uniprot-TrEMBL)
RAF1GeneProduct5894 (Entrez Gene)
RAP1AGeneProduct5906 (Entrez Gene)
RAP1BGeneProduct5908 (Entrez Gene)
RAPGEF1GeneProduct2889 (Entrez Gene)
RASA1GeneProduct5921 (Entrez Gene)
RB_HUMANProteinP06400 (Uniprot-TrEMBL)
RHEB_HUMANProteinQ15382 (Uniprot-TrEMBL)
RICTORProtein253260 (Entrez Gene)
RPTOR_HUMANProteinQ8N122 (Uniprot-TrEMBL)
SMAD2_HUMANProteinQ15796 (Uniprot-TrEMBL) Tumor supressor
SMAD3_HUMANProteinP84022 (Uniprot-TrEMBL)
SMARCA4GeneProduct6597 (Entrez Gene)
SMARCC1GeneProduct6599 (Entrez Gene)
SMARCC2GeneProduct6601 (Entrez Gene)
SMARCD1GeneProduct6602 (Entrez Gene)
SMARCD2GeneProduct6603 (Entrez Gene)
SMARCD3GeneProduct6604 (Entrez Gene)
SOS1GeneProduct6654 (Entrez Gene) Son of sevenless homolog 1 (Drosophila) (predicted)
SP1Protein6667 (Entrez Gene) DNA licensing factor for AR. Frequently occupies regions in enhancers with DNA recognition elements close to AR ARE
SPINK1GeneProduct6690 (Entrez Gene)
  • From Entrez Gene: The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis
  • Association with Prostate Cancer - Chinnaiyan Lab Cancer Cell Paper - ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
SPINK1ProteinD6RIU5 (Uniprot-TrEMBL)
SPRY1GeneProduct10252 (Entrez Gene)
SPRY2GeneProduct10253 (Entrez Gene)
STAT1_HUMANProteinP42224 (Uniprot-TrEMBL)
STAT3GeneProduct6774 (Entrez Gene)
SWI/SNFComplex
Steroid-19-HydroxylaseGeneProductENSG00000120054 (Ensembl)
TMPRSS2GeneProduct7113 (HGNC)
TRANSLATION
TSC1_HUMANProteinQ92574 (Uniprot-TrEMBL)
TSC2_HUMANProteinP49815 (Uniprot-TrEMBL)
TestosteroneMetabolite58-22-0 (CAS)
dehydroepiandrosteroneMetabolite53-43-0 (CAS)
p13KProtein
p14Protein
p15Protein
p21Protein
p27Protein
p38GeneProductENSG00000112062 (Ensembl)

Annotated Interactions

No annotated interactions

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